Continental J.

Pharmaceutical Sciences 4: 51 - 55, 2010 ISSN: 2141 - 4149

© Wilolud Journals, 2010 http://www.wiloludjournal.com

TABLETING PROPERTIES OF ACID MODIFIED CASSAVA STARCH DEHYDRATED IN ALCOHOL

Achor, M.1, Oyi, A.R2 and Isah, A.B2

1
Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu
Danfodiyo University, Sokoto, Nigeria, 2Department of Pharmaceutics and Pharmaceutical Microbiology,
Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.

ABSTRACT
The work was aimed to investigate the suitability of acid modified cassava starch (ACS) dehydrated in
ethanol for use as filler/binder in direct compression. ACS was obtained by acid hydrolysis using
hydrochloric acid at both 6.0 N and 8.0 N for 24 and 18 respectively. Powders retained on 150 µm sieve
were used in tablet formulation. Tablets were made using metronidazole (200mg) in a ratio 1:1 using
the direct compression method. The results obtained showed that there was a significant increase in
dissolution rate, crushing and tensile strength with reduced friability of ACS as compared to their native
form. Generally, ACS showed increase dissolution rate profile and lower disintegration time as
compared to microcrystalline cellulose which showed a superior crushing and tensile strength.

KEYWORDS: cassava starch, microcrystalline cellulose, acid hydrolysis, metronidazole, filler/binder.

INTRODUCTION
Cassava starch has many remarkable characteristics including high paste viscosity, high paste clarity and high
freeze-thaw stability, in particular, the native starch with high purity can be readily modified by physical,
chemical and enzymatic process to many diversified products to improve the starch functionality and
consequently, encourage more industrial application. The simplest and most common starch modification is by
acid hydrolysis which is widely used in food, paper, textile and pharmaceutical industries (Karntarat et al,
2008). Acid modification changes the physicochemical properties of starch without destroying its granular
structure (Singh and Ali, 2000). It has been established that acid modified starch obtains improved properties as
Tableting excipient if the starch product obtained is first dehydrated by means of a water-miscible organic
solvent and the resulting starch product dried. The thus obtained starch powder has an increased specific surface
area and, with respect to binding force and breaking strength, have improved properties as Tableting excipients
(Buwalda and Willemina, 1997).

Acid treatment can cause a breakdown of the polymeric structure in cassava powder to obtain a less elastic but a
more plastic material which is amenable to direct compression (Florence and Roland, 2002). Recent advances in
formulation technologies have lead to a shift from traditional wet granulation to direct compression
manufacturing process in the development of solid oral dosage forms due largely to process expedition, easy
handling, and time and cost savings (Nyström and Glazer, 1985). Tableting excipients are classified according
to their functional properties such as binder, fillers, disintegrants, lubricants, flavors and coloring agents.
Suitable starch products may also perform several functions, such as the combination of filler and binder (often
designated as filler/binder). In this study, acid modified cassava starch dehydrated in alcohol was evaluated for
its suitability as a filler/binder in direct compression and subsequently compared with native cassava starch and
microcrystalline cellulose (Avicel PH 101).

MATERIALS AND METHODS

Materials
Ethanol 96% (BDH Chemicals Ltd, Poole England), concentrated hydrochloric acid and sodium hydroxide
(May and Baker Laboratory Chemical, Dagenham, England), metronidazole powder (Vingesh International
Limited, India), microcrystalline cellulose PH 101 (ATOZ Pharmaceuticals Limited, Ambaltur, India)

Production of acid modified starch

Production of acid modified cassava starch was carried out as described by Buwalda and Willemina (1997). 450
grams of an aqueous suspension of starch (36% w/v wt starch) was poured into a stainless steel vessel. To this
suspension, 28ml, 6N and 8N HCL was added drop-wise with stirring. Subsequently the reaction was conducted
for 18 and 24 hours respectively at 50oC. After cooling, the modified starch product was separated from the
reaction medium by filtration. On the filtrate, the separated starch product was washed 1:1 with water, then the
starch product was suspended again in 250ml water and brought to pH 6 with sodium hydroxide solution. The

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starch product was separated by means of filtration with 750ml water. A sample of 100g of the wet starch
product separated by filtration was suspended in 800ml ethanol and stirred for 30 minutes. Subsequently, the
starch product was separated by filtration and dried in Gallenkamp hot air oven (Philips Harris Ltd, England) at
40oC. The dried starch was ground to fine powder and those fraction retained on 150µm sieve were used for
further studies.

Preparation of tablets
An Erweka tableting press (Erweka apparatebau GmbH, Germany) fitted with a 10.0 mm punch tip diameter
was used. Metronidazole tablets were formulated using the direct compression method at a ratio 1:1 with
cassava starch, acid modified starches and microcrystalline cellulose (MCC PH101) as excipients with 0.5 %
magnesium stearate as lubricant at a pressure setting of 9 metric tones using the following formula

Table 1: Formula for metronidazole tablets

Formulation Metronidazole Mag. St. CS ACS6 ACS8 MCC
(mg) (mg) (mg) (mg) (mg) (mg)
F1 200 2.0 200 _ _ _
F2 200 2.0 _ 200 _ _
F3 200 2.0 _ _ 200 _
F4 200 2.0 _ _ _ 200
KEY
CS = cassava starch, ACS6 = acid modified cassava starch using 6N HCl for 24 hrs, ACS8 = acid modified v
cassava starch using 8N HCl for 18 hrs

EVALUATION OF TABLETS
Uniformity of weight
Ten tablets were weighed individually and collectively from each batch using Metler P163 balance (Zurich,
Switzerland) and the mean weights computed. The percent coefficient of tablet weight variation (% CV) was
calculated according to the formula (Bolhuis, 1988)

% CV = standard deviation/mean weight……………. (1).

Density of tablets
Densities of tablets at corresponding pressure loads were used to evaluate compressibility. Tablet density was
obtained from the weight of compact and its volume as follows:

Relative density (g/ml) = weight of tablet (g) / tablet volume (ml)………. (2)

The volume of tablet was calculated from the relationship:

Volume of tablet = Πr2tρ ……………….. (3)

Where r = radius of tablet, and
t = tablet thickness
ρ = particle density of the granules

Crushing strength
The Monsanto hardness tester was used to determine the crushing strength of five tablets from each batch
twenty-four hours to allow enough time for elastic recovery to occur after the tablets had been compressed.

Tensile strength
The radial tensile strength Ts of tablets was calculated from the equation:

Ts = 2F / Πdt ……………………….. (4)

Where, F = load needed to break the tablet,
d = diameter of tablets
t = tablet thickness

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Friability test
Ten tablets were dusted, weighed together and subjected to abrasion test in the Erweka TA3R friabilator
(Erweka apparatebau GmbH, Germany) operated at 25 rpm for 4 minutes. The tablets were then dusted properly
and weighed again collectively. The difference in weight was then determined and expressed as percentage
friability value.

Disintegration time studies

The disintegration time of tablets was determined with Erweka disintegration apparatus (ZT3), (Erweka
apparatebau GmbH, Germany) using the BP (2004) method. Water thermostatically maintained at 37o ± 0.5oC
was the medium. The time taken for all of the six tablets, one placed in each of the six tubes of the apparatus to
disintegrate and pass through the mesh was recorded using a stop clock.

Dissolution tests
Erweka disintegration apparatus ZT3 (Erweka apparatebau GmbH, Germany) was utilized using the basket
method. One tablet was placed in the dry basket and lowered into the dissolution medium (0.1 N HCl) half way
before the rotation began at a speed of 100 rpm. 10 ml of the sample was withdrawn from half way between the
surface of the dissolution medium and the top of the rotating basket at 10 minutes interval for one hour. After
every withdrawal, 10 ml of the medium was replaced. A one in ten dilution with the dissolution media was made
before the absorbance of the sample was taken at 277 nm with Genesys 20 spectrophotometer (Madison,
Wisconsin, USA).

Statistical analysis
Statistical analysis was done to compare the crushing and tensile strength of the formulation between MCC
PH101, cassava starch and acid modified starches using the t-test. At 95% confidence interval, ρ value lower or
equal to 0.05 was considered the limit of significance.

RESULTS AND DISCUSSIONS

Wight uniformity of metronidazole tablets can be attributed to the flow characteristics of the excipients with
MCC PH101 known to have a poor flow properties as compared to acid modified cassava starch (Achor et al,
2010). The density of the tablets also reflects the densities of the excipients as reported by Achor et al (2010).
The results of friability test for metronidazole tablets as shown in Table 2 shows that MCC PH 101 had better
friability value (F4) as compared to cassava starch and its modified products (F1,F2 and F3). This can be
attributed to the crushing strength of the tablets. Disintegration of tablets can be considered as the result of two
processes; water uptake and the separation of the particles due to elastic expansion of the compressed particles
and annihilation of the interparticulate hydrogen bonds followed by penetration of water between the particles
(Michael, 2006). The more compact a tablet is, the less the porosity and hence less penetration of water into the
tablet and as a result, longer disintegration time. All starch types for metronidazole tablets passed the BP (2004)
specification for disintegration of uncoated tablets (within 15 min) except MCC PH 101. This can be attributed
to the stronger bonds coupled with the impairment of swelling ability by better compressibility of MCC PH 101.
This retards water penetration and cause tablet rupture less readily.

Table 2: Properties of metronidazole tablets

Parameters F1 F2 F3 F4
Wt. uniformity 1.48 1.89 1.96 2.80
(%coefficient)
Density (g/cm3) 1.19 (1.12) 1.17 (0.35) 1.20 (0.84) 0.96 (1.20)
Disintegration (min.) 8.00 (0.08) 11.00 (0.12) 16.00 (0.10) 40.00 (0.45)
Friability (%) 3.61 (0.05) 2.98 (0.03) 2.21 (0.02) 2.12 (0.02)
*value is mean and standard deviation is in parenthesis, number of replicate = 3
KEY: F1, F2, F3 and F4 represents metronidazole tablets formulated using CS, ACS6, ACS8 and MCC PH101
respectively as excipients.

Metronidazole tablets formulated using acid modified cassava starch showed tablets with higher crushing and
tensile strengths as compared to its native from (Fig. 1) The crushing strength of a tablet, like its thickness, is a
function of the die fill and compression force. In an ideal situation, at a constant die fill, the crushing strength
values increase and thickness decreases as additional compression force is applied. Metronidazole tablets

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formulated using MCC PH 101 gave tablets with better crushing strength as compared to cassava starch. There
was a statistical significant difference at P< 0.05 between MCC PH 101 and modified cassava starch. Also,
between both batches of modified cassava starch, there was no statistical significant difference at P< 0.05.

Fig. 1: Crushing and tensile strength of metronidazole tablets

Fig. 2 shows the dissolution profiles of metronidazole tablets. The t50% (time taken for 50 % of the drug to be
released) and t90% (time taken for 90 % of the drug to be released) were below 25 minutes except for tablet
formulated using MCC PH 101 (F4). This can be attributed to its crushing strength. For metronidazole tablets,
F1, F2 and F3 passed the BP (2004) specification for dissolution profile for uncoated tablet which states that 75
% of the drug should be released within 45 minutes. The monitoring of tablets crushing strength is especially
important for drug products that possess real or potential bioavailability problems or that are sensitive to altered
dissolution release profiles as a function of the compressive force employed.

Fig. 2: Dissolution profile of metronidazole tablets

CONCLUSION
It can be seen that metronidazole tablets formulated with acid modified cassava starch showed improved
tableting properties as compared to its native starch. MCC PH101 showed better friability, crushing and tensile
strength as compared to cassava starch and its modified products, but in terms of its disintegration and
dissolution profile, if attainment of high peak blood levels for the drug is a product objective, obtaining rapid
drug dissolution from the tablet as seen with the modified cassava starch will be critically important.

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REFERENCES
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Buwalda, P.L. and Willemina, A.A. (1997). U. S. Patent WO/1997/031627.

British Pharmacopoeia (2004). HMSO, London.

Florence, E. E. and Roland, S. O. (2002). Effect of acid treatment on the consolidation and plasto-elasticity of
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Karntarat, W., Sujin, S., Wannapong, T. and Darapond, T. (2008). Amylose/Amylopectin simple determination
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Michael, L. (2006). A cellulose based product and its interaction with water; Ph.D (Pharmaceutics) thesis work,
Institute of Pharmaceutical Technology, University of Basel, Switzerland. pp 91

Nyström, C. and Glazer, M. (1985). Studies on direct compression of tablets. XIII. The effect of some dry
binders on the tablet strength of compounds with different fragmentation propensity. Int J Pharm. 23:255-263.

Singh, V. and Ali, S.Z. (2000). Acid degradation of starch, the effect of acid and starch type. Carbohyr. Polym,
41: 191-195.

Received for Publication: 07/10/2010

Accepted for Publication: 19/12/2010

Corresponding Author
Achor, M
Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu
Danfodiyo University, Sokoto, Nigeria

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